The objective of the proposed research is to define the mechanism by which bacterial endotoxin mitigates the reactivity of transplanted immunocompetent murine spleen cells against normal mouse tissues without abolishing their capacity to kill tumor cells. In the planned experiments, we will compare graded doses of spleen cells from endotoxin related and untreated histoincompatible donor mice for graft-versus-host (GVH) reactivity in immunosuppressed adult mice; study the reactivity of histoincompatible immunocompetent cells from endotoxin treated donor mice against AKR spontaneous leukemia using a bioassay system; attempt to gain insight into possible mechanisms by which endotoxin lessens GVH reactivity; test splenic subpopulations for suppressor cell activity; test the effect of serum from endotoxin treated mice on GVH reactivity of normal spleen cells; determine whether in vitro incubation can substitute for in vivo treatment with endotoxin; and use histoincompatible immunocompetent cells treated with endotoxin for adoptive immunotherapy of advanced spontaneous leukemia in AKR mice. The planned study should contribute significant information regarding the immunological reaction against cancer and help elucidate successful approaches to the immunotherapy of malignancy.